Effects of rifampin-based antituberculosis therapy on plasma efavirenz concentrations in children vary by CYP2B6 genotype.
Effects of rifampin-based antituberculosis therapy on plasma efavirenz concentrations in children vary by CYP2B6 genotype.
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DOI：
10.1097/qad.0b013e328360dbb4
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发表时间：
2013-07-31
期刊：
影响因子：
--
通讯作者：
Maartens G
中科院分区：
文献类型：
--
作者：
McIlleron HM;Schomaker M;Ren Y;Sinxadi P;Nuttall JJ;Gous H;Moultrie H;Eley B;Merry C;Smith P;Haas DW;Maartens G
An efavirenz-based antiretroviral therapy (ART) regimen is preferred for children more than 3 years of age with tuberculosis. However, rifampin, a key component of antituberculosis therapy, induces CYP2B6. An increased dose of efavirenz is recommended in adults weighing more than 50 kg who require rifampin, but there is scant information in children being treated for tuberculosis. Plasma efavirenz concentrations were compared in 40 children during concomitant treatment for tuberculosis and HIV-1, after stopping rifampicin, and in a control group of children without tuberculosis. Associations with antituberculosis treatment, metabolizer genotype (based on CYP2B6 516G→T, 983T→C, and 15582C→T), weight, and time after dose were evaluated. Compared to children with extensive metabolizer genotypes, efavirenz concentrations were increased 1.42-fold (95% confidence interval, CI 0.94–2.15) and 2.85-fold (95% CI 1.80–4.52) in children with intermediate and slow metabolizer genotypes, respectively. Concomitant antituberculosis treatment increased efavirenz concentrations 1.49-fold (95% CI 1.10–2.01) in children with slow metabolizer genotypes, but did not affect efavirenz concentrations in extensive or intermediatemetabolizer genotypes. After adjustment for dose/kg, each kilogram of weight was associated with a 2.8% (95% CI 0.9–4.7) decrease in efavirenz concentrations. Despite higher milligram per kilogram doses, a higher proportion of children in the lowest weight band (10–13.9 kg) had efavirenz concentrations less than 1.0 mg/l than larger children. Antituberculosis treatment was not associated with reduced efavirenz concentrations in children, which does not support increased efavirenz doses. Children with slow metabolizer genotype have increased efavirenz concentrations during antituberculosis treatment, likely due to isoniazid inhibiting enzymes involved in accessory metabolic pathways for efavirenz.
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影响因子：
2.3
作者：
Shah, Ira;Swaminathan, Soumya;Lala, Mamatha
通讯作者：
Lala, Mamatha
影响因子：
158.5
作者：
Starr, SE;Fletcher, CV;Mofenson, LM
通讯作者：
Mofenson, LM
影响因子：
2.6
作者：
di Iulio, Julia;Fayet, Aurelie;Telenti, Amalio
通讯作者：
Telenti, Amalio
DOI：
10.1056/nejmoa1011214
发表时间：
2011-07-07
期刊：
The New England journal of medicine
影响因子：
--
作者：
Madhi SA;Nachman S;Violari A;Kim S;Cotton MF;Bobat R;Jean-Philippe P;McSherry G;Mitchell C;P1041 Study Team
通讯作者：
P1041 Study Team
DOI：
10.1097/qai.0b013e318235e560
发表时间：
2011-12-01
影响因子：
3.6
作者：
Fillekes, Quirine;Natukunda, Eva;Walker, A. Sarah
通讯作者：
Walker, A. Sarah